Modulation of endocrine nuclear receptor activities by polyaromatic compounds present in fractionated extracts of diesel exhaust particles

0507732 - BFÚ 2020 RIV NL eng J - Journal Article
Pěnčíková, K. - Cigánek, M. - Neca, J. - Illes, P. - Dvořák, Z. - Vondráček, Jan - Machala, M.
Modulation of endocrine nuclear receptor activities by polyaromatic compounds present in fractionated extracts of diesel exhaust particles.
Science of the Total Environment. Roč. 677, AUG 10 2019 (2019), s. 626-636. ISSN 0048-9697. E-ISSN 1879-1026
R&D Projects: GA ČR(CZ) GA16-17085S
Institutional support: RVO:68081707
Keywords : aryl-hydrocarbon receptor * polycyclic aromatic-hydrocarbons * estrogen-receptor * cell-line * in-vitro
OECD category: Ecology
Impact factor: 6.551, year: 2019
Method of publishing: Limited access
https://www.sciencedirect.com/science/article/pii/S0048969719319357?via%3Dihub

Organic pollutants associated with diesel exhaust particles (DEP), such as polycyclic aromatic hydrocarbons (PAHs) and their derivatives, may negatively impact human health. However, a comprehensive overview of their effects on endocrine nuclear receptor activities is still missing. Here, we evaluated the effects of extracts and chromatographic fractions (fractionated according to increasing polarity) of two standard reference materials derived from distinct types of diesel engines (SRM 2975, SRM 1650b), on activation of androgen receptor (AR), estrogen receptor alpha (ER alpha), peroxisome proliferator-activated receptor gamma (PPAR gamma), glucocorticoid receptor (GR) and thyroid receptor alpha (TR alpha), using human cell-based reporter gene assays. Neither DEP standard modulated AR or GR activities. Crude extracts and fractions of SRM 1650b and SRM 2975 suppressed ER alpha-mediated activity in the ER-CALUX (TM) assay, however, this effect could be partly linked to their cytotoxicity in this cell line. We observed that only SRM 2975 extract and its fractions were partial PPAR gamma inducers, while SRM 1650b extract was not active towards this receptor. Importantly, we found that both extracts and polar fractions of SRM activated TR alpha and significantly potentiated the activity of endogenous TR alpha ligand, triiodothyronine. Based on a detailed chemical analysis of both extracts and their polar fractions, we identified several oxygenated PAH derivatives, that were present at relatively high levels in the analyzed DEP standards, including 3-nitrobenzanthrone (3-NBA), anthracene-9,10-dione, phenanthrene-9,10-dione. 9H-fluoren-9-one or benzo[a] anthracene-7,12-dione, to activate TR alpha activity. Nevertheless, these compounds provided only a minor contribution to the overall TR alpha activity identified in polar fractions. This suggests that yet unidentified polar polyaromatic compounds associated with DEP may, apart from their known impact on the aryl hydrocarbon receptor or steroid signaling, deregulate activities of additional nuclear receptors, in particular of TR alpha. This illustrates the need to better characterize endocrine disrupting activities of DEP. (C) 2019 Elsevier B.V. All rights reserved.
Permanent Link: http://hdl.handle.net/11104/0298708